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Biomedical subjects

M Imai

Publications and source records attributed to M Imai.

At least 37 records · Page 2Linked to original sources

Protein kinase C and phosphatidylinositol 3-kinase independently contribute to P-glycoprotein-mediated drug secretion in the mouse proximal tubule.

We have recently reported that the apical membrane of the proximal tubule S2 segment from wild-type mice (WT mice) has the capacity for P-glycoprotein- (P-gp-) mediated drug efflux, whereas mice in which both mdr1a and mdr1b genes are disrupted (KO mice) do not. To examine the intracellular regulatory mechanisms of drug-transporting P-gp activity, we isolated and perfused proximal tubule S2 segments from WT and KO mice, and measured luminal efflux of the intracellular fluorescence of rhodamine 123, a fluorescent substrate of P-gp. The decay half-time of the intracellular fluorescence (t1/2) was regarded as an index of the drug-transporting P-gp activity. In the WT mice, the t1/2 was 36+/-5 s (n=35) during the basal period, and was significantly increased to 440+/-45 s by the luminal addition of verapamil (an inhibitor of P-gp). The addition of phorbol 12-myristate 13-acetate (PMA) [a protein kinase C (PKC) activator] to the bath increased t1/2, but 4alpha-phorbol (the inactive form of PMA) did not. The PMA-induced increase in t1/2 was further increased by the luminal addition of verapamil, and was partially inhibited by co-treatment with staurosporine or H-7 (inhibitors of PKC). Pretreatment with wortmannin or LY294002 [inhibitors of phosphatidylinositol 3-kinase (PI 3-kinase)] added to the bath also increased t1/2. The wortmannin- and LY294002-induced increase in t1/2 was also further increased by the luminal addition of verapamil. The effects of PMA on t1/2 were additive after cotreatment with wortmannin or LY294002. In the KO mice, t1/2 was 440+/-25 s (n=18) during the basal period, and was no longer affected by the addition of verapamil, staurosporine, H-7, wortmannin, or LY294002. Based on the use of pharmacological agents, we conclude that in the proximal tubule from WT mice, P-gp-mediated drug secretion occurs independently via PKC- and PI 3-kinase-dependent processes, whereas it is not present in KO mice, independently of PKC- and PI 3-kinase.

ATP Binding Cassette Transporter, Subfamily B↗

Optical coherence tomography of tractional macular elevations in eyes with proliferative diabetic retinopathy.

PURPOSE: To document the findings of optical coherence tomography in eyes with tractional macular elevation associated with proliferative diabetic retinopathy, paying special attention to differentiating between tractional retinal detachment and retinoschisis. DESIGN: Observational case series. METHODS: We retrospectively reviewed images of optical coherence tomography obtained from 17 consecutive eyes (17 patients) with proliferative diabetic retinopathy without vitreous opacity and showing tractional macular elevation with or without foveal involvement. RESULTS: Tractional retinal detachment and retinoschisis could be differentiated in the cross-sectional images of optical coherence tomography. Retinoschisis with or without associated retinal detachment was observed in 16 of 17 eyes (94%), whereas retinal detachment was observed in only six of 17 eyes (35%). Five eyes showed both findings of retinal detachment and retinoschisis. CONCLUSIONS: Optical coherence tomography is useful for distinguishing tractional retinoschisis from retinal detachment in eyes with proliferative diabetic retinopathy and macular elevation. Tractional retinoschisis with or without retinal detachment is the most frequent pattern of tractional macular elevation in eyes with proliferative diabetic retinopathy.

Adult↗

Optical coherence tomography of tractional macular elevations in eyes with proliferative diabetic retinopathy.

PURPOSE: To document the findings of optical coherence tomography in eyes with tractional macular elevation associated with proliferative diabetic retinopathy, paying special attention to differentiating between tractional retinal detachment and retinoschisis. DESIGN: Observational case series. METHODS: We retrospectively reviewed images of optical coherence tomography obtained from 17 consecutive eyes (17 patients) with proliferative diabetic retinopathy without vitreous opacity and showing tractional macular elevation with or without foveal involvement. RESULTS: Tractional retinal detachment and retinoschisis could be differentiated in the cross-sectional images of optical coherence tomography. Retinoschisis with or without associated retinal detachment was observed in 16 of 17 eyes (94%), whereas retinal detachment was observed in only six of 17 eyes (35%). Five eyes showed both findings of retinal detachment and retinoschisis. CONCLUSIONS: Optical coherence tomography is useful for distinguishing tractional retinoschisis from retinal detachment in eyes with proliferative diabetic retinopathy and macular elevation. Tractional retinoschisis with or without retinal detachment is the most frequent pattern of tractional macular elevation in eyes with proliferative diabetic retinopathy.

Adult↗

Significance of fetal fibronectin and cytokine measurement in the cervicovaginal secretions of women at term in predicting term labor and post-term pregnancy.

OBJECTIVE: To determine whether fetal fibronectin (FFN) or cytokine concentrations in cervicovaginal secretions can be used to predict term labor and post-term pregnancy. STUDY DESIGN: FFN and cytokines were assayed in cervicovaginal mucus from 122 pregnant women at 29-35 weeks and weekly from week 36 to parturition. RESULTS: FFN concentrations were elevated from about 3 weeks before parturition; a correlation was found between FFN levels and sampling-to-delivery intervals. Parturition was best predicted within 7 days of sampling when the FFN value was >or=50ng/ml between 36 and 41 gestational weeks. Interleukin-1beta (IL-1beta) concentrations were elevated from 3 to 4 weeks before parturition; a correlation was found between IL-1beta levels and sampling-to-delivery intervals. Parturition was best predicted within 7 days of sampling, with an IL-1beta cut-off value of >or=100pg/ml. CONCLUSION: Term labor and post-term pregnancy can be predicted within 7 days of sampling, using FFN and IL-1beta concentrations in cervicovaginal secretions of pregnant women.

Adult↗

Intravitreal phacoemulsification with pars plana vitrectomy and posterior chamber intraocular lens suture fixation for dislocated crystalline lenses.

This technique to manage a dislocated crystalline lens comprises intravitreal phacoemulsification with transscleral suture fixation of a posterior chamber intraocular lens (IOL). The dislocated lens in the vitreous cavity is removed using a standard phaco handpiece with the assistance of a fiber-optic light pipe. Then, the IOL is implanted. The technique was used in 10 eyes of 8 patients with lens luxation or subluxation. The postoperative best corrected visual acuity was 20/25 or better except in 1 eye, and no serious complications were observed. Increased intraocular pressure before surgery in 4 eyes was normalized in 3 eyes.

Aged↗

Inactivity and muscle: effect of resistance training during bed rest on muscle size in the lower limb.

The present study aimed to investigate the effect of dynamic leg press training on the physiological cross-sectional areas (PCSAs) of human lower limb muscles during 20 days of 6 degrees head-down tilt bed rest. Five healthy men comprised the resistance training group (BR-Tr) and data from two previous studies were used to derive a 10-man control group (BR-Cont). The BR-Tr performed two sessions (morning and afternoon session) of dynamic leg press action including knee extension and plantar flexion daily for the bed rest period: (1) three sets of 10 repetitions at 90% of maximum load and (2) 40% of maximum load to exhaustion. The PCSAs of the knee extensor (KE), knee flexor (KF), plantar flexor (PF), and dorsiflexor muscle groups were estimated using serial axial magnetic resonance (MR) images of the right-thigh and leg. After the bed rest period, the BR-Tr showed a significant increase in the PCSA of the KE. Although PCSA of the KF in two groups significantly decreased after bed rest, percentage of change in PCSA of the biceps femoris (long head) and semitendinosus muscles in the BR-Tr, which occupied approximately 70% of the KF, was significantly higher than those in the BR-Cont. Both the BR-Tr and BR-Cont groups showed significant decreases in the PCSA of PF with similar magnitude of 11.6% (P < 0.001) and 11.9% (P < 0.001), respectively. These results suggest that dynamic leg press training during bed rest can prevent deteriorating of the KE and a part of KF, but not the calf muscles.

Adult↗

"Avian-type" renal medullary tubule organization causes immaturity of urine-concentrating ability in neonates.

BACKGROUND: While neonatal kidneys are not powerful in concentrating urine, they already dilute urine as efficiently as adult kidneys. To elucidate the basis for this paradoxical immaturity in urine-concentrating ability, we investigated the function of Henle's loop and collecting ducts (IMCDs) in the inner medulla of neonatal rat kidneys. METHODS: Analyses of individual renal tubules in the inner medulla of neonatal and adult rat kidneys were performed by measuring mRNA expression of membrane transporters, transepithelial voltages, and isotopic water and ion fluxes. Immunofluorescent identification of the rCCC2 and rCLC-K1 using polyclonal antibodies was also performed in neonatal and adult kidney slices. RESULTS: On day 1, the transepithelial voltages (V(Ts)) in the thin ascending limbs (tALs) and IMCDs were 14.6 +/- 1.1 mV (N = 27) and -42.7 +/- 6.1 mV (N = 14), respectively. The V(Ts) in the thin descending limbs (tDLs) were zero on day 1. The V(Ts) in the tALs were strongly inhibited by luminal bumetanide or basolateral ouabain, suggesting the presence of a NaCl reabsorption mechanism similar to that in the thick ascending limb (TAL). The diffusional voltage (V(D)) of the tAL due to transepithelial NaCl gradient was almost insensitive to a chloride channel blocker 5-nitro-2-(3-phenylpropylamino)-benzoate (NPPB). The V(Ts) in the IMCDs were strongly inhibited by luminal amiloride. On day 1, both the tDL and tAL were impermeable to water, indicating the water impermeability of the entire loop. Diffusional water permeability (P(dw)) and urea permeabilities (P(urea)) in the IMCDs indicated virtual impermeability to water and urea on day 1. Stimulation by vasopressin (1 nmol/L) revealed that only P(dw) was sensitive to vasopressin by day 14. A partial isoosmolar replacement of luminal urea by NaCl evoked negligible water flux across the neonatal IMCDs, indicating the absence of urea-dependent volume flux in the neonatal IMCD. These transport characteristics in each neonatal tubule are similar to those in quail kidneys. Identification of mRNAs and immunofluorescent studies for specific transporters, including rAQP-1, rCCC2, rCLC-K1, rENaC beta subunit, rAQP-2, and rUT-A1, supported these findings. CONCLUSION: We hypothesize that the renal medullary tubule organization of neonatal rats shares a tremendous similarity with avian renal medulla. The qualitative changes in the organization of medullary tubules may be primarily responsible for the immature urine-concentrating ability in mammalian neonates.

Age Factors↗

Targeting platelet aggregation: CD39 gene transfer augments nucleoside triphosphate diphosphohydrolase activity in injured rabbit arteries.

BACKGROUND: CD39, the major endothelial nucleoside triphosphate diphosphohydrolase (NTPDase), plays an important role in local thromboregulation. We hypothesized that balloon injury (BI) leads to an acute reduction in arterial NTPDase activity that could be restored by a targeted gene delivery strategy. METHODS: Recombinant adenoviral vectors containing human CD39 (Ad-CD39) or beta-galactosidase (Ad-LacZ) were used. Endothelial (ECs) and smooth muscle cells (SMCs) were infected in vitro and NTPDase activity measured. New Zealand white rabbits (N = 28) underwent bilateral iliofemoral artery balloon injury, followed by incubation with Ad-CD39, Ad-LacZ, or vehicle. Explanted vessels were analyzed for NTPDase activity and localization of CD39 expression by immunohistochemistry. Deposition of fluorescent-labeled platelets was studied 3 days after injury and vector treatment. RESULTS: In vitro, Ad-CD39 infection resulted in a greater than 40-fold increase in adenosine diphosphatase activity in ECs and a 3-fold increase in SMCs. In vivo, CD39 transgene expression localized to the luminal aspect of Ad-CD39--treated vessels. BI resulted in an acute reduction in vessel wall NTPDase activity (P <.05). Ad-CD39 augmented NTPDase activity when compared with vehicle or Ad-LacZ (P <.05). Platelet deposition on the injured arterial surface was modest and not different between Ad-CD39-- and Ad-LacZ--treated vessels. CONCLUSIONS: BI decreases native NTPDase activity, which can be augmented by adenovirus-mediated gene transfer of CD39. Further studies are required to determine whether targeted delivery of CD39 could convey thromboprotective properties to an injured vessel.

Acid Anhydride Hydrolases↗

Arterial and venous Thrombelastograph variables differ during cardiac surgery.

UNLABELLED: The Thrombelastograph (TEG; Haemoscope Corp., Skokie, IL) coagulation analyzer is an effective point-of-care monitor for routine clinical practice and clinical research. Prior investigators have used either arterial or venous samples of blood for TEG measurements. We conducted this prospective cohort study to determine potential differences in TEG variables between arterial and venous blood samples. Arterial and venous samples were drawn from 40 cardiac surgical patients, yielding 134 pairs for comparison. Twenty-nine comparisons (control) were between arterial and arterial samples and were not significantly different. For the arterial and venous comparisons (n = 105), mean (+/-sd) arterial and venous values were the following: reaction time, 10 +/- 2 mm vs 13 +/- 4 mm, P = 0.004; maximum amplitude, 59 +/- 9 mm vs 49 +/- 12 mm, P < 0.001; alpha angle, 61 +/- 10 degrees vs 51 +/- 14 degrees, P < 0.001; K, 5 +/- 2 mm vs 8 +/- 4 mm, P = 0.007; and lysis, 2.5 +/- 1.7 vs 2.5 +/- 2.0 (not significant), arterial versus venous, respectively. Arterial blood samples demonstrated TEG values reflecting stronger (larger maximum amplitude) and faster (shorter reaction time and K value, wider alpha angle) clot formation. The results suggest that users of TEG coagulation analyzers should be consistent with the site of blood sampling given the potential differences obtained. IMPLICATIONS: Thrombelastograph (TEG) values obtained from venous blood samples differ from values obtained from arterial blood samples. When the TEG coagulation analyzer is used for clinical purposes, it is important to be consistent in the blood collection site.

Adult↗

Matrix metalloproteinases in human diabetic and nondiabetic vitreous.

PURPOSE: To compare matrix metalloproteinase (MMP) activities in human vitreous samples from patients with diabetic retinopathy (DR) and other vitreoretinal diseases, and to investigate the factors influencing the MMP activities in human DR vitreous samples. METHODS: Thirty-one diabetic and 17 nondiabetic vitreous samples (from nine patients with macular holes and eight patients with epiretinal membranes) were examined. Samples collected at the time of pars plana vitrectomy were subjected to substrate zymography to conduct a quantitative analysis of MMP activity. Immunoblotting against antihuman MMP-1, 2, and 9 was performed to identify MMP in vitreous samples. The effects of posterior vitreous detachment (PVD), vitreous hemorrhage, proliferative membrane, traction detachment, and cystoid macular edema on MMP activities were investigated. RESULTS: All vitreous samples from both DR and non-DR patients showed a single band at the position of 72 kD, corresponding to MMP-2. Another band at 99 kD, corresponding to MMP-9, was detected significantly more often in DR samples than in non-DR samples: 45.2% and 0%, respectively (P = 0.0007). The number of samples showing a band from MMP-9 was significantly higher in partial PVD samples than in complete PVD samples: 66.7% and 15.4%, respectively (P = 0.001). CONCLUSION: The results indicated that MMP-9 may be involved in DR and that partial PVD may be related to the MMP-9 activity in DR.

Adult↗

[Evaluation of an HIV screening assay kit for the combined detection of anti-HIV-1/2 antibodies and HIV p24 antigen].

We have evaluated a new HIV screening assay kit (Genscreen HIV Ag-Ab) for the HIV antigen-antibody combined test by comparing with two HIV antigen-antibody combined assay kits (VIDAS HIV DUO, Enzygnost HIV integral). Genscreen HIV Ag-Ab is a microwell plate enzyme immunoassay for the detection of HIV infection, based on the detection of anti-HIV-1/2 antibodies and HIV p24 antigen in human serum or plasma. In this study, 90 samples of HIV-1 antibody positive sera and 670 samples of HIV negative sera were examined. The sensitivity was 100% and the specificity was 99.7%. All of HIV-1 group M sera (subtypes A to G and B/D), HIV-1 group O sera and HIV-2 sera in worldwide HIV performance panel-302 were positive with Genscreen HIV Ag-Ab. Ten commercially available HIV-1 seroconversion panels were tested to evaluate sensitivity of three HIV antigen-antibody combined assay kits. Genscreen HIV Ag-Ab detected infection at the same bleeds as VIDAS HIV DUO in 8 of 10 seroconversion panels and 1 to 2 bleeds earlier than Enzygnost HIV integral in 5 of 10 seroconversion panels. However, VIDAS HIV DUO indicated false negative on 5th bleed in panel BB (PRA952). The result of the specimen was positive on 3rd bleed, equivocal on 4th bleed, negative on 5th bleed and again positive on 6th bleed. All of these specimens were positive by Genscreen HIV Ag-Ab. Therefore, Genscreen HIV Ag-Ab that shorten the window period is a useful and reliable for HIV screening test, especially in case of primary infection.

AIDS Serodiagnosis↗

[Evaluation of immunochromatography method for rapid detection of influenza A and B viruses].

We have evaluated a new rapid detection kit for influenza A and B viruses, known as the QuickVue Influenza test (Quidel Coporation, USA); which is based on immunochromatography using virus isolates and clinical specimens. Twelve strains of influenza A and B were tested for evaluate the reactivity and detection limits of this test. The QuickVue Influenza test showed a positive result for all twelve strains of influenza virus and a negative result for fourteen different kinds of other respiratory viruses. The detection limits for six strains were 5 to 30 pfu/ml for a cell culture, 1.0 x 10(3) to 6.0 x 10(4) pfu/ml for 1st PCR, 1 to 50 pfu/ml for nested PCR, 3.0 x 10(5) to 6.0 x 10(5) pfu/ml for the QuickVue Influenza test, 1.5 x 10(5) to 1.0 x 10(6) pfu/ml for the Directigen Flu A, and 7.5 x 10(5) to 5.0 x 10(6) pfu/ml for the FLU OIA. Furthermore, the QuickVue Influenza test were clinically evaluated using 92 throat swab specimens collected from patients with influenza-like illnesses. By cell culture, influenza viruses were detected in 49 of the 92 specimens (AH1N1: 20, AH3N2: 7, B: 22); the titers of the influenza viruses were between 2.5 pfu/ml and 7.0 x 10(5) pfu/ml. Compared to cell culture, the QuickVue Influenza test showed a sensitivity of 75.5%, a specificity of 93.0%, a positive predictive value of 92.5%, a negative predictive value of 76.9%, and an efficiency value of 83.7%. On the other hand, influenza viruses were detected in 54 of the 92 specimens (AH1N1: 19, AH 3N2: 10, B: 25) by RT-PCR. Compared to RT-PCR, the QuickVue Influenza test showed a sensitivity of 72.2%, a specificity of 97.4%, a positive predictive value of 97.5%, a negative predictive value of 71.2%, and an efficiency value of 82.6%. Overall, only one throat swab specimen produced a false positive result using the QuickVue Influenza test; thus, this test appears to have a high specificity. We conclude that the QuickVue Influenza test is a simple one-step test with a sensitivity and specificity equivalent to those of other conventional diagnostic kits. The test is useful and suitable for the diagnosis of influenza and for identifying influenza patients requiring antiviral therapy.

Influenza A virus↗

Troglitazone stimulates basolateral rheogenic Na+/HCO3- cotransport activity in rabbit proximal straight tubules.

Thiazolidinedione derivatives, new insulin-sensitizing antidiabetic agents, are expected to have potential clinical use. Since these drugs cause edema in a variable proportion of patients, we examined whether troglitazone (Tro) has direct action on Na+ transport of rabbit proximal straight tubule perfused in vitro. For this purpose, we measured basolateral membrane voltage (V(B)) by conventional microelectrode techniques and intracellular pH (pH(i)) by microscopic fluorescence spectrophotometry with a pH-sensitive fluorescent dye, 2', 7'-bis-2-carboxyethyl-5-carboxyfluorescein. Tro at 50 microM in the bath significantly depolarized both transepithelial voltage and V(B). To examine whether the basolateral rheogenic Na+/HCO3- cotransport activity is affected by Tro, we observed V(B) deflection upon abrupt 10-fold decrease in bath HCO3- in the absence and presence of Tro. The apparent transference number of HCO3- (tHCO3), as calculated from the V(B) deflection, was significantly greater in the presence of Tro (50 microM) than that seen in its absence. Tro caused cell acidification and increased the intracellular acidification rates (dpH(i)/dt) upon abrupt 10-fold decreases in bath HCO3- and Na+ concentrations. The stimulatory effects of Tro on tHCO3 and dpH(i)/dt were dose dependent between 5 and 50 miccroM, but they were unaffected at 0.5 microM. From these results, we conclude that Tro acts on the proximal straight tubule and stimulates the basolateral rheogenic Na+/HCO3- cotransport activity. The stimulatory action of Tro may partly account for edema formation.

Acidosis↗

Congenital giant aneurysm of the left atrial appendage mimicking pericardial absence case report.

A 25-year-old man was found to have an abnormal cardiac contour on a chest radiograph, and was referred. Transesophageal echocardiography suggested herniation of the left atrial appendage (LAA) through a gap in the pericardium, and magnetic resonance imaging indicated congenital partial absence of the pericardium. Cardiac dysfunction was caused by compression from the enlarged left atrium and thrombi were thought to be present in the appendage, so surgery was performed. The intraoperative diagnosis was congenital LAA aneurysm. Although distinguishing between congenital LAA aneurysm and congenital absence of the pericardium is reported to be possible with magnetic resonance imaging, we were unable to so in this case.

Adult↗

[A case of multiple sclerosis with recurrent episodes of psychiatric symptoms].

We reported a 19-year-old woman with multiple sclerosis (MS) with recurrent episodes of psychiatric symptoms at the age of 10 and 19, as the first and 11th relapse, respectively. Her first episode of MS resembled acute encephalitis at the age of 9 and she relapsed 12 times. The psychiatric symptoms were not mood disorders but altered states of consciousness, such as the delirous state. She was treated with high doses of intravenous methylpredonisolone and her symptoms were almost resolved, but her anxiety neurosis remained. Her MRI showed demyelination in the white matter of the frontal lobe and the hippocampus, which suggested that psychiatric symptoms of MS would be related to the frontal lobe lesion.

Adult↗

[Anesthesia for a patient with cardiac sarcoidosis].

Anesthesia for a 49-year-old man with cardiac sarcoidosis is reported. Preoperative cardiac examination showed left ventricular dysfunction (ejection fraction = 27%) and myocardial conduction defects. In addition, his previous history included atrial fibrillation and cerebral infarction. Transesophageal echocardiography showed thrombus in the left appendage. Anesthesia was induced with fentanyl and diazepam and maintained with fentanyl and isoflurane. Perioperative hemodynamic monitoring included direct arterial pressure, central venous and pulmonary artery pressure and continuous cardiac output. In addition, transesophageal echocardiography was useful for watching thrombus in the left appendage. His hemodynamic condition was stable and no neurological complication was noted after anesthesia.

Anesthesia, General↗